tbuckley/cabot-search huggingface dataset:
Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy
Authors: Linda Reinhard, Maya Machalitza, Thorsten Wiech, Hermann-Josef Gröne, Moritz Lassé, Markus M. Rinschen, Nicoletta Ferru, Jan Hinrich Bräsen, Friederike Drömann, Peter Maria Rob, Sanjeev Sethi, Elion Hoxha, Rolf A.K. Stahl
Journal: Journal of the American Society of Nephrology (2022)

Primary membranous nephropathy (MN) is caused by circulating autoantibodies binding to antigens on the podocyte surface. PLA2R1 is the main target antigen in 70%-80% of cases, but the pathogenesis is unresolved in 10%-15% of patients.We used native western blotting to identify IgG4 autoantibodies, which bind an antigen endogenously expressed on podocyte membranes, in the serum of the index patient with MN. These IgG4 autoantibodies were used to immunoprecipitate the target antigen, and mass spectrometry was used to identify Netrin G1 (NTNG1). Using native western blot and ELISA, NTNG1 autoantibodies were analyzed in cohorts of 888 patients with MN or other glomerular diseases.NTNG1 was identified as a novel target antigen in MN. It is a membrane protein expressed in healthy podocytes. Immunohistochemistry confirmed granular NTNG1 positivity in subepithelial glomerular immune deposits. In prospective and retrospective MN cohorts, we identified three patients with NTNG1-associated MN who showed IgG4-dominant circulating NTNG1 autoantibodies, enhanced NTNG1 expression in the kidney, and glomerular IgG4 deposits. No NTNG1 autoantibodies were identified in 561 PLA2R1 autoantibodies-positive patients, 27 THSD7A autoantibodies-positive patients, and 77 patients with other glomerular diseases. In two patients with available follow-up of 2 and 4 years, both NTNG1 autoantibodies and proteinuria persisted.NTNG1 expands the repertoire of target antigens in patients with MN. The clinical role of NTNG1 autoantibodies remains to be defined.
Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance
Authors: Johannes Holle, Hendrik Bartolomaeus, Ulrike Löber, Felix Behrens, Theda U.P. Bartolomaeus, Harithaa Anandakumar, Moritz I. Wimmer, Dai Long Vu, Mathias Kuhring, Ulrike Brüning, Andras Maifeld, Sabrina Geisberger, Stefan Kempa, Fabian Schumacher, Burkhard Kleuser, Philip Bufler, Uwe Querfeld, Stefanie Kitschke, Denise Engler, Leonard D. Kuhrt, Oliver Drechsel, Kai-Uwe Eckardt, Sofia K. Forslund, Andrea Thürmer, Victoria McParland, Jennifer A. Kirwan, Nicola Wilck, Dominik Müller
Journal: Journal of the American Society of Nephrology (2022)

CKD is characterized by a sustained proinflammatory response of the immune system, promoting hypertension and cardiovascular disease. The underlying mechanisms are incompletely understood but may be linked to gut dysbiosis. Dysbiosis has been described in adults with CKD; however, comorbidities limit CKD-specific conclusions.We analyzed the fecal microbiome, metabolites, and immune phenotypes in 48 children (with normal kidney function, CKD stage G3-G4, G5 treated by hemodialysis [HD], or kidney transplantation) with a mean±SD age of 10.6±3.8 years.Serum TNF-α and sCD14 were stage-dependently elevated, indicating inflammation, gut barrier dysfunction, and endotoxemia. We observed compositional and functional alterations of the microbiome, including diminished production of short-chain fatty acids. Plasma metabolite analysis revealed a stage-dependent increase of tryptophan metabolites of bacterial origin. Serum from patients on HD activated the aryl hydrocarbon receptor and stimulated TNF-α production in monocytes, corresponding to a proinflammatory shift from classic to nonclassic and intermediate monocytes. Unsupervised analysis of T cells revealed a loss of mucosa-associated invariant T (MAIT) cells and regulatory T cell subtypes in patients on HD.Gut barrier dysfunction and microbial metabolite imbalance apparently mediate the proinflammatory immune phenotype, thereby driving the susceptibility to cardiovascular disease. The data highlight the importance of the microbiota-immune axis in CKD, irrespective of confounding comorbidities.
A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb2
Authors: Ichiro Hada, Akira Shimizu, Hiromu Takematsu, Yukino Nishibori, Toru Kimura, Toshiyuki Fukutomi, Akihiko Kudo, Noriko Ito-Nitta, Zentaro Kiuchi, Jaakko Patrakka, Naoaki Mikami, Simon Leclerc, Yoshihiro Akimoto, Yoshiaki Hirayama, Satoka Mori, Tomoko Takano, Kunimasa Yan
Journal: Journal of the American Society of Nephrology (2022)

The cause of podocyte injury in idiopathic nephrotic syndrome (INS) remains unknown. Although recent evidence points to the role of B cells and autoimmunity, the lack of animal models mediated by autoimmunity limits further research. We aimed to establish a mouse model mimicking human INS by immunizing mice with Crb2, a transmembrane protein expressed at the podocyte foot process.C3H/HeN mice were immunized with the recombinant extracellular domain of mouse Crb2. Serum anti-Crb2 antibody, urine protein-to-creatinine ratio, and kidney histology were studied. For signaling studies, a Crb2-expressing mouse podocyte line was incubated with anti-Crb2 antibody.Serum anti-Crb2 autoantibodies and significant proteinuria were detected 4 weeks after the first immunization. The proteinuria reached nephrotic range at 9-13 weeks and persisted up to 29 weeks. Initial kidney histology resembled minimal change disease in humans, and immunofluorescence staining showed delicate punctate IgG staining in the glomerulus, which colocalized with Crb2 at the podocyte foot process. A subset of mice developed features resembling FSGS after 18 weeks. In glomeruli of immunized mice and in Crb2-expressing podocytes incubated with anti-Crb2 antibody, phosphorylation of ezrin, which connects Crb2 to the cytoskeleton, increased, accompanied by altered Crb2 localization and actin distribution.The results highlight the causative role of anti-Crb2 autoantibody in podocyte injury in mice. Crb2 immunization could be a useful model to study the immunologic pathogenesis of human INS, and may support the role of autoimmunity against podocyte proteins in INS.
Donor natural killer cells trigger production of β-2-microglobulin to enhance post–bone marrow transplant immunity
Authors: Loredana Ruggeri, Elena Urbani, Davide Chiasserini, Federica Susta, Pier Luigi Orvietani, Emanuela Burchielli, Sara Ciardelli, Rosaria Sola, Stefano Bruscoli, Antonella Cardinale, Antonio Pierini, Sander R. Piersma, Stefano Pasquino, Franco Locatelli, Dunia Ramarli, Enrico Velardi, Luciano Binaglia, Connie R. Jimenez, Georg A. Holländer, Andrea Velardi
Journal: Blood (2022)
Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats
Authors: Karin Bergling, Giedre Martus, Carl M. Öberg
Journal: Journal of the American Society of Nephrology (2022)

Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis (PD). We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during PD in rats. However, more recently, we found that phlorizin, a dual blocker of sodium glucose cotransporters 1 and 2, reduces glucose diffusion in PD. Therefore, either inhibiting sodium glucose cotransporter 1 or blocking facilitative glucose channels by phlorizin metabolite phloretin would reduce glucose transport in PD.We tested a selective blocker of sodium glucose cotransporter 1, mizagliflozin, as well as phloretin, a nonselective blocker of facilitative glucose channels, in an anesthetized Sprague-Dawley rat model of PD.Intraperitoneal phloretin treatment reduced glucose absorption by >30% and resulted in a >50% higher ultrafiltration rate compared with control animals. Sodium removal and sodium clearances were similarly improved, whereas the amount of ultrafiltration per millimole of sodium removed did not differ. Mizagliflozin did not influence glucose transport or osmotic water transport.Taken together, our results and previous results indicate that blockers of facilitative glucose channels may be a promising target for reducing glucose absorption and improving ultrafiltration efficiency in PD.
The psychosis metabolic risk calculator (PsyMetRiC) for young people with psychosis: International external validation and site-specific recalibration in two independent European samples
Authors: Benjamin I. Perry, Frederik Vandenberghe, Nathalia Garrido-Torres, Emanuele F. Osimo, Marianna Piras, Javier Vazquez-Bourgon, Rachel Upthegrove, Claire Grosu, Victor Ortiz-Garcia De La Foz, Peter B. Jones, Nermine Laaboub, Miguel Ruiz-Veguilla, Jan Stochl, Celine Dubath, Manuel Canal-Rivero, Pavan Mallikarjun, Aurélie Delacrétaz, Nicolas Ansermot, Emilio Fernandez-Egea, Severine Crettol, Franziska Gamma, Kerstin J. Plessen, Philippe Conus, Golam M. Khandaker, Graham K. Murray, Chin B. Eap, Benedicto Crespo-Facorro
Journal: The Lancet Regional Health - Europe (2022)

Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors.
Comparison of safety and effectiveness between laparoscopic and open pancreatoduodenectomy: A systematic review and meta-analysis
Authors: Taoyuan Yin, Tingting Qin, Kongyuan Wei, Ming Shen, Zhenxiong Zhang, Jingjing Wen, Shutao Pan, Xingjun Guo, Feng Zhu, Min Wang, Hang Zhang, Mohammad Abu Hilal, Renyi Qin
Journal: International Journal of Surgery (2022)

Validity of the laparoscopic approach in pancreatic head lesion remains debatable. This study aims to compare the safety and effectiveness of laparoscopic pancreatoduodenectomy (LPD) and open pancreatoduodenectomy (OPD) and investigate the source of heterogeneity from surgeons' and patients' perspectives. We searched PubMed, Cochrane, Embase, and Web of Science for studies published before February 1, 2021. Of 6578 articles, 81 were full-text reviewed. The primary outcome was mortality. Three independent reviewers screened and extracted the data and resolved disagreements by consensus. Studies were evaluated for quality using ROB2.0 and ROBINS-I. According to different study designs, sensitivity and meta-regression analyses were conducted to explore the heterogeneity source. This meta-analyses was also conducted to explore the learning curve's heterogeneity. This study was registered with PROSPERO, CRD42021234579. We analyzed 34 studies involving 46,729 patients (4705 LPD and 42,024 OPD). LPD was associated with lower (P = 0.025) in unmatched studies (P = 0.017). No differences in mortality existed in randomized controlled trials (P = 0.854) and matched studies (P = 0.726). Sensitivity analysis found no significant difference in mortality in elderly patients, patients with pancreatic cancer, and in high- and low-volume hospitals (all P > 0.05). In studies at the early period of LPD (<40 cases), higher mortality (P < 0.001) was found (all P < 0.05).LPD showed non-inferiority in length of stay, complications, and survival outcomes in all analyses. In high-volume centers with adequate surgical experience, LPD in selected patients appears to be a valid alternative to LPD with comparable mortality, LOS, complications, and survival outcomes.
Assessing, Controlling, and Assuring the Quality of Medical Information on the Internet
Authors: William M. Silberg
Journal: JAMA (1997)

Health care professionals and patients alike should view with equal parts delight and concern the exponential growth of the Internet (the Net), and especially its graphical, user-friendly subset, the World Wide Web (the Web), as a medical information delivery tool.<sup>1,2</sup>Delight because the Internet hosts a large number of high-quality medical resources and poses seemingly endless opportunities to inform, teach, and connect professionals and patients alike. Concern because the fulfillment of that promise remains discouragingly distant. Technical glitches aside, when it comes to medical information, the Internet too often resembles a cocktail conversation rather than a tool for effective health care communication and decision making. See also p 1258. The problem is not too little information but too much, vast chunks of it incomplete, misleading, or inaccurate, and not only in the medical arena.<sup>3,4</sup>The Net—and especially the Web—has the potential to become the world's largest vanity press.
Hand and foot dermatitis in patients referred for patch testing: Analysis of North American Contact Dermatitis Group Data, 2001-2018
Authors: Jonathan I. Silverberg, Nisha Patel, Erin M. Warshaw, Joel G. DeKoven, Donald V. Belsito, Amber Reck Atwater, Marie-Claude Houle, James S. Taylor, Margo J. Reeder, Kathryn A. Zug, Denis Sasseville, Vincent A. DeLeo, Melanie D. Pratt, Joseph F. Fowler, Howard I. Maibach
Journal: Journal of the American Academy of Dermatology (2022)
Prefrontal cortex as a key node in arousal circuitry
Authors: George A. Mashour, Dinesh Pal, Emery N. Brown
Journal: Trends in Neurosciences (2022)

The role of the prefrontal cortex (PFC) in the mechanism of consciousness is a matter of active debate. Most theoretical and empirical investigations have focused on whether the PFC is critical for the content of consciousness (i.e., the qualitative aspects of conscious experience). However, there is emerging evidence that, in addition to its well-established roles in cognition, the PFC is a key regulator of the level of consciousness (i.e., the global state of arousal). In this opinion article we review recent data supporting the hypothesis that the medial PFC is a critical node in arousal-promoting networks.
A global horizon scan for urban evolutionary ecology
Authors: Brian C. Verrelli, Marina Alberti, Simone Des Roches, Nyeema C. Harris, Andrew P. Hendry, Marc T.J. Johnson, Amy M. Savage, Anne Charmantier, Kiyoko M. Gotanda, Lynn Govaert, Lindsay S. Miles, L. Ruth Rivkin, Kristin M. Winchell, Kristien I. Brans, Cristian Correa, Sarah E. Diamond, Ben Fitzhugh, Nancy B. Grimm, Sara Hughes, John M. Marzluff, Jason Munshi-South, Carolina Rojas, James S. Santangelo, Christopher J. Schell, Jennifer A. Schweitzer, Marta Szulkin, Mark C. Urban, Yuyu Zhou, Carly Ziter
Journal: Trends in Ecology & Evolution (2022)
Growth and differentiation of human induced pluripotent stem cell (hiPSC)-derived kidney organoids using fully synthetic peptide hydrogels
Authors: Niall J. Treacy, Shane Clerkin, Jessica L. Davis, Ciarán Kennedy, Aline F. Miller, Alberto Saiani, Jacek K. Wychowaniec, Dermot F. Brougham, John Crean
Journal: Bioactive Materials (2022)

Human induced pluripotent stem cell (hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine. However, there remains a necessity to refine the biophysical and biochemical parameters that govern kidney organoid formation. Differentiation within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and maturation. Here, we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels (SAPHs) of variable stiffness (storage modulus, G'). The resulting organoids contained complex structures comparable to those differentiated within the animal-derived matrix, Matrigel. Single-cell RNA sequencing (scRNA-seq) was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface. A total of 13,179 cells were analysed, revealing 14 distinct clusters. Organoid compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids, while SAPH-derived organoids were enriched for stromal-associated cell populations. Notably, differentiation within a higher G' SAPH generated podocytes with more mature gene expression profiles. Additionally, maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types, which are a known limitation of current kidney organoid protocols. This work demonstrates the utility of synthetic peptide-based hydrogels with a defined stiffness, as a minimally complex microenvironment for the selected differentiation of kidney organoids.
Targeted intervention to achieve waste reduction in gastrointestinal endoscopy
Authors: João A Cunha Neves, Joana Roseira, Patrícia Queirós, Helena Tavares Sousa, Gianluca Pellino, Miguel F Cunha
Journal: Gut (2022)

Endoscopy is healthcare's third largest generator of medical waste in hospitals. This prospective study aimed to measure a single unit's waste carbon footprint and perform a pioneer intervention towards a more sustainable endoscopy practice. The relation of regulated medical waste (RMW; material fully contaminated with blood or body fluids or containing infectious agents) versus landfill waste (non-recyclable material not fully contaminated) may play a critical role.In a four-stage prospective study, following a 4-week observational audit with daily weighing of both waste types (stage 1), stage 2 consisted of a 1-week intervention with team education of waste handling. Recycling bins were placed in endoscopy rooms, landfill and RMW bins were relocated. During stages 3 (1 month after intervention) and 4 (4 months after intervention), daily endoscopic waste was weighed. Equivalence of 1 kg of landfill waste to 1 kg carbon dioxide equivalent (CO2e) and 1 kg of RMW to 3kgCO2e was assumed. Paired samples t-tests for comparisons.From stage 1 to stage 3, mean total waste and RMW were reduced by 12.9% (p=0.155) and 41.4% (p=0.010), respectively, whereas landfill (p=0.059) and recycling waste increased (paper: p=0.001; plastic: p=0.007). While mean endoscopy load was similar (46.2 vs 44.5, p=0.275), a total decrease of CO2e by 31.6% (138.8kgCO2e) was found (mean kgCO2e109.7 vs 74.9, p=0.018). The annual reduction was calculated at 1665.6kgCO2e. All these effects were sustained 4 months after the intervention (stage 4) without objections by responsible endoscopy personnel.In this interventional study, applying sustainability measures to a real-world scenario, RMW reduction and daily recycling were achieved and sustained over time, without compromising endoscopy productivity.
Assessment of Adherence to Reporting Guidelines by Commonly Used Clinical Prediction Models From a Single Vendor
Authors: Jonathan H. Lu, Alison Callahan, Birju S. Patel, Keith E. Morse, Dev Dash, Michael A. Pfeffer, Nigam H. Shah
Journal: JAMA Network Open (2022)

Various model reporting guidelines have been proposed to ensure clinical prediction models are reliable and fair. However, no consensus exists about which model details are essential to report, and commonalities and differences among reporting guidelines have not been characterized. Furthermore, how well documentation of deployed models adheres to these guidelines has not been studied.
Comprehensive Analysis of Fibroblast Activation Protein Expression in Interstitial Lung Diseases
Authors: Penghui Yang, Qun Luo, Xinlu Wang, Qi Fang, Zhenli Fu, Jia Li, Yunxin Lai, Xiaobo Chen, Xin Xu, Xiaomin Peng, Kongzhen Hu, Xiaowei Nie, Shaoyu Liu, Jinhe Zhang, Junqi Li, Chenyou Shen, Yingying Gu, Jianping Liu, Jingyu Chen, Nanshan Zhong, Jin Su
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Section:ChooseTop of pageAbstract <<Study DesignMethodsResultsDiscussionReferencesCITING ARTICLES
Effects of Patient-Driven Lifestyle Modification Using Intermittently Scanned Continuous Glucose Monitoring in Patients With Type 2 Diabetes: Results From the Randomized Open-label PDF Study
Authors: Hun Jee Choe, Eun-Jung Rhee, Jong Chul Won, Kyong Soo Park, Won-Young Lee, Young Min Cho
Journal: Diabetes Care (2022)

OBJECTIVE To investigate the effects of patient-driven lifestyle modification using intermittently scanned continuous glucose monitoring (isCGM) in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We conducted a 12-week, open-label, randomized controlled trial. A total of 126 participants were 1:1 randomized to either the intervention group (structured education + isCGM) or the control group (standard care with blood glucose monitoring). The Self-Evaluation Of Unhealthy foods by Looking at postprandial glucose (SEOUL) algorithm was developed and applied to aid structured education in guiding patients to follow healthy eating behavior depending on the postprandial glycemic response. The primary end point was the change in HbA1c level from baseline. RESULTS Implementation of the SEOUL algorithm with isCGM was associated with greater improvement in HbA1c than with standard care (risk-adjusted difference −0.50%, 95% CI −0.74 to −0.26, P &amp;lt; 0.001). Participants in the intervention group had a greater reduction in fasting blood glucose and body weight (−16.5 mg/dL, 95% CI −30.0 to −3.0, P = 0.017; −1.5 kg, 95% CI −2.7 to −0.3, P = 0.013, respectively). The score sum for the Korean version of the revised Summary of Diabetes Self-Care Activities Questionnaire increased in both groups but to a greater extent in the intervention group (mean difference 4.8, 95% CI 1.7–8.0, P = 0.003). No severe hyperglycemia or hypoglycemia was reported in either group of patients. CONCLUSIONS Patient-driven lifestyle modification primarily focused on eating behavior using isCGM effectively lowered HbA1c levels in patients with T2D.
Recommending Healthy Diet and Exercise to Patients With Parkinson Disease—No Reason to Hold Back
Authors: Beate R. Ritz, Kimberly C. Paul
Journal: JAMA Network Open (2022)

Xinyuan Zhang, PhD; Samantha A. Molsberry, PhD; Michael A. Schwarzschild, MD, PhD; Alberto Ascherio, MD, DrPH; Xiang Gao, MD, PhD
Association of Methamphetamine and Opioid Use With Nonfatal Overdose in Rural Communities
Authors: P. Todd Korthuis, Ryan R. Cook, Canyon A. Foot, Gillian Leichtling, Judith I. Tsui, Thomas J. Stopka, Judith Leahy, Wiley D. Jenkins, Robin Baker, Brian Chan, Heidi M. Crane, Hannah L. Cooper, Judith Feinberg, William A. Zule, Vivian F. Go, Angela T. Estadt, Robin M. Nance, Gordon S. Smith, Ryan P. Westergaard, Brent Van Ham, Randall Brown, April M. Young
Journal: JAMA Network Open (2022)

Overdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities.